title: Anti-rejection prophylaxis by blocking selectin dependent cell adhesion after rat allogeneic and xenogeneic lung transplantation.
abstract: OBJECTIVE
  Adhesion molecules regulate the infiltration of leukocytes into the graft during rejection after lung transplantation. The first step of the adhesion cascade is mediated by selectins. Sialyl-LewisX is a ligand of P-selectin. The purpose of the study was to evaluate SLX, a synthetic oligosaccharide analog of Sialyl-LewisX, for anti-rejection prophylaxis after allogeneic and xenogeneic left lateral, orthotopic rat lung transplantation.
  
  
  METHODS
  In groups A and B, allogeneic lung transplantation was performed using fully incompatible rat strains (donors: Dark-Agouti (RT1a); recipients: Lewis (RT11)). In group A (n = 10), recipients recieved 200 microg/d SLX i.v. on day 0-4. Group B rats (n = 10) served as untreated controls. The animals were sacrificed on days 5 and 10, respectively. In groups C and D, xenogenic lung transplantation was performed using Gold Syrian hamsters as donors and Lewis rats as recipients. In group C (n = 10), recipients received 200 microg/d SLX i.v. on day 0-4. Group D rats (n = 10) served as untreated controls. The animals were sacrificed on days 2 and 5, respectively. Rejection was graded by histology from 0 (no rejection) to 5 (necrosis). By immunhistology, alveolar, interstitial CD11a, CD18 and VLA-4 positive leukocytes were counted.
  
  
  RESULTS
  Histologically, there were a lower grade of rejection (A: 2.7 +/- 0.6; B: 4.0 +/- 0.0; P < 0.05) and fewer CD11a positive leukocytes (A: 66 +/- 27; B: 186 +/- 73; P < 0.05) on day 5 in the SLX-treated allograft group compared to the untreated group. In xenotransplantation, SLX also reduced the grade of rejection (C: 3.3 +/- 0.5; D: 4.7 +/- 0.5; P < 0.05) and the number of CD11a positive leukocytes (C: 145 +/- 22; D: 176 +/- 20; P < 0.05) on day 2.
  
  
  CONCLUSIONS
  It is concluded, that the administration of SLX significantly reduces allograft rejection. After discontinuation treatment with SLX unmodified rejection appeared. SLX also modifies xenograft rejection, but to a lesser extent, and xenograft necrosis appeared during treatment in this model.
authors.affiliation: Department of Thoracic and Cardiovascular Surgery, Hannover Medical School, Germany.
authors.forename: M
authors.initials: M
authors.lastname: Brandt
authors.forename: G
authors.initials: G
authors.lastname: Derner
authors.forename: K
authors.initials: K
authors.lastname: Boeke
authors.forename: M L
authors.initials: ML
authors.lastname: Phillips
authors.forename: G
authors.initials: G
authors.lastname: Steinhoff
authors.forename: A
authors.initials: A
authors.lastname: Haverich
mesh_terms: D000818:Animals; D018821:CD18 Antigens / Q000032:analysis; D006224:Cricetinae; D006084:Graft Rejection / Q000517:prevention & control*; D039041:Integrin alpha4beta1; D016023:Integrins / Q000032:analysis; D007962:Leukocytes / Q000276:immunology; D016040:Lung Transplantation; D016169:Lymphocyte Function-Associated Antigen-1 / Q000032:analysis; D008297:Male; D008647:Mesocricetus; D009844:Oligosaccharides / Q000494:pharmacology*; D019007:P-Selectin / Q000276:immunology*; D051381:Rats; D011919:Rats, Inbred Strains; D016201:Receptors, Lymphocyte Homing / Q000032:analysis; D000080506:Sialyl Lewis X Antigen; D014183:Transplantation, Heterologous; D014184:Transplantation, Homologous
chemical_list: D018821:CD18 Antigens; D039041:Integrin alpha4beta1; D016023:Integrins; D016169:Lymphocyte Function-Associated Antigen-1; D009844:Oligosaccharides; D019007:P-Selectin; D016201:Receptors, Lymphocyte Homing; D000080506:Sialyl Lewis X Antigen